Abstract Serious non-variceal upper gastrointestinal bleeding (NVUGIB) is a major cause of morbidity and mortality worldwide. Incidence of NVUGIB in the US is close to 50 events per 100,000 adults, with approximately 160,000 hospital admissions annually. US treatment and prevention of NVUGIB continues to be a major medical emergency, costing 550-900 million dollars every year. Failure in standard of care for NVUGIB results in mortality rates from 3-4% in the US. An improved hemostatic approach to NVUGIB will significantly reduce hemorrhage related morbidity and mortality with reduced cost of hospital care. The ideal device would be nontoxic; able to be stored for 2 years without refrigeration; be easily deployed; provide immediate hemostasis for difficult to control brisk & pulsatile bleeding; allow successful low accuracy/acuity placement in a bleeding obscured surgical field; not require significant follow-up or removal; and dissolve or be digested in the gastric cavity in under 7 days. This proposal addresses finalization in development of such a device. To address serious NVUGIB, Tricol Biomedical & Oregon Health & Science University propose to finalize development of a foldable, highly efficacious, chitosan gastrointestinal hemostatic dressing (CGHD) with wire delivery (WD) via a standard endoscope working channel. The primary objective of this research proposal is to complete development of a novel efficacious CGHD+DW and its management of challenging acute GI bleeding in the gastric environment that can be left in place to be fully digested or dissolved in less than 168 hours. The final CGHD+WD device will be validated in a 7-day study of a large animal model of brisk, pulsatile UGIB to support an investigational device exemption (IDE) for a Phase I clinical study. The central hypothesis of this Phase II proposal is that the finalized CGHD+DW with delivery through the standard endoscope working channel will provide effective, immediate and sustained hemostasis for brisk NVUGIB.